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Series GSE208440 Query DataSets for GSE208440
Status Public on Oct 16, 2023
Title Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for euploid (EU79) and down syndrome (DS) brain organoids with Choroid plexus (CP) upon infection with SARS-CoV-2.
 
Contributor(s) Slonchak A
Citation(s) 38838150
Submission date Jul 18, 2022
Last update date Jun 26, 2024
Contact name Andrii Slonchak
E-mail(s) a.slonchak@uq.edu.au
Phone 61733653302
Organization name The University of Queensland
Department School Of Chemistry And Molecular Biosciences
Street address MBS Bldg 76, Cooper Rd
City St Lucia
State/province QLD
ZIP/Postal code 4072
Country Australia
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (12)
GSM6346479 Euploid human brain organoids, uninifected 1
GSM6346480 Euploid human brain organoids, uninifected 2
GSM6346481 Euploid human brain organoids, uninifected 3
Relations
BioProject PRJNA859925

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Supplementary file Size Download File type/resource
GSE208440_Count_matrix.txt.gz 528.5 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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